PBRM1 loss promotes PD-L1 secretion in renal cell carcinoma cells through TNF-α/exosome signaling axis
10.3969/j.issn.1009-8291.2023.01.015
- VernacularTitle:PBRM1缺失通过TNF-α/exosome信号轴促进肾癌细胞PD-L1分泌
- Author:
Hongjun XIE
1
;
Xiaoyun GU
2
;
Ke WANG
1
;
Yanlin JIAN
1
;
Lei LI
1
;
Dalin HE
1
;
Shan XU
1
Author Information
1. Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an 710061; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi’an Jiaotong University, Xi’an 710061
2. Shaanxi Health Information Center, Health Commission of Shaanxi Province, Xi’an 710061, China
- Publication Type:Journal Article
- Keywords:
renal cell carcinoma;
PBRM1;
exosome;
PD-L1;
immunotherapy
- From:
Journal of Modern Urology
2023;28(1):65-70
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the expressions of PBRM1 and PD-L1 in renal cell carcinoma (RCC), and the molecular mechanism of PBRM1 regulating PD-L1, in order to provide experimental results for clinical immunotherapy. 【Methods】 The protein expressions of PBRM1 and PD-L1 were detected with immunohistochemistry, and their mRNA expressions were determined by analyzing TCGA database. Meanwhile, the relationship between overall survival and mRNA expressions of PBRM1 and PD-L1 were analyzed in TCGA database. The exosomes were extracted with exoEasy Maxi Kit. Expressions of exosomal biomarkers CD63 and CD9 were detected with Western blotting, and their morphology was observed with transmission electron microscope. PD-L1 expression after IFN-γ, IL-6 and TNF-α treatment was detected with Western blotting. 【Results】 The expression of PBRM1 was significantly lower in canver tissue than in paracancerous tissue (P<0.001). The loss rate of PBRM1 was up to 76.4%. PBRM1 expression was not correlated with PD-L1 expression. PBRM1 deletion activated TNF-α/exosome signaling pathway, leading to increase of PD-L1 secretion in exosomes, which was then transported to the outside of cells. 【Conclusion】 There is no relationship between PBRM1 and PD-L1 protein expressions in RCC. However, PBRM1 mutation can lead to inflammatory signaling pathway activation, inducing PD-L1 secretion, which is encapsulated in exosomes and transported to the outside of cells, and affects the response of immunotherapy.
